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Curcumin Alleviates Sepsis‐Associated Acute Kidney Injury Potentially by Inhibiting Ferroptosis Through the ACSL4/GPX4 Signaling Pathway

Year: 2025

Type: article

Abstract: ABSTRACT This study aimed to investigate the protective effect of curcumin against sepsis‐associated acute kidney injury (SA‐AKI) in vitro and in vivo, and to clarify the role of ferroptosis in this protection. Human renal tubular epithelial cell (RTEC) line HK‐2 was stimulated with lipopolysaccharide (LPS). Ferroptosis was further induced with erastin. In vivo, a rat SA‐AKI model was produced by cecal ligation and puncture (CLP) and allocated to the Sham, sepsis, and curcumin (Cur) + sepsis (Sep) groups. Glutathione (GSH), malondialdehyde (MDA), and pro‐inflammatory cytokines were quantified by ELISA. Western blot analysis was used to evaluate the ferroptosis‐related proteins, including long‐chain acyl‐coenzyme synthetases 4 (ACSL4) and glutathione peroxidase 4 (GPX4). Apoptosis of RTECs was assessed with TUNEL staining, and ultrastructural changes were examined by transmission electron microscopy (TEM). Compared with the Sepsis group, the Cur + Sep group showed significantly lower Paller damage scores, reduced Scr, BUN, TNF‐α, IL‐1β, IL‐6, MDA, Fe 2+ levels, and ACSL4 protein expression (all p < 0.05). Conversely, GSH and GPX4 levels were significantly elevated in the Cur + Sep group (both p < 0.05). TUNEL staining revealed fewer apoptotic RTECs in the Cur + Sep group compared with the Sepsis group ( p < 0.05). TEM demonstrated swollen mitochondria with condensed membranes and vanished cristae in the sepsis group, changes that were markedly alleviated by curcumin. In HK‐2 cells, erastin abolished curcumin's protective effect against LPS‐induced injury. Curcumin attenuates SA‐AKI, likely by suppressing inflammation and ferroptosis via the ACSL4/GPX4 signaling pathway.

Source: Drug Development Research

DOI: 10.1002/ddr.70181

Authors: Lifeng Wang, Nannan Wu, Weidong Zhang, Die Huang, Yongning Li

Institutions: Dalian Medical University, First Affiliated Hospital of Dalian Medical University

Language: English

Topic: Acute Kidney Injury Research

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,980